| First Author | Emrich SM | Year | 2023 |
| Journal | Elife | Volume | 12 |
| PubMed ID | 36803766 | Mgi Jnum | J:345485 |
| Mgi Id | MGI:7579505 | Doi | 10.7554/eLife.84708 |
| Citation | Emrich SM, et al. (2023) Orai3 and Orai1 mediate CRAC channel function and metabolic reprogramming in B cells. Elife 12 |
| abstractText | The essential role of store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels in T cells is well established. In contrast, the contribution of individual Orai isoforms to SOCE and their downstream signaling functions in B cells are poorly understood. Here, we demonstrate changes in the expression of Orai isoforms in response to B cell activation. We show that both Orai3 and Orai1 mediate native CRAC channels in B cells. The combined loss of Orai1 and Orai3, but not Orai3 alone, impairs SOCE, proliferation and survival, nuclear factor of activated T cells (NFAT) activation, mitochondrial respiration, glycolysis, and the metabolic reprogramming of primary B cells in response to antigenic stimulation. Nevertheless, the combined deletion of Orai1 and Orai3 in B cells did not compromise humoral immunity to influenza A virus infection in mice, suggesting that other in vivo co-stimulatory signals can overcome the requirement of BCR-mediated CRAC channel function in B cells. Our results shed important new light on the physiological roles of Orai1 and Orai3 proteins in SOCE and the effector functions of B lymphocytes. |
